To enhance our understanding of plant cells as systems, there is a need to emphasize studies on individual cell types and individual cells of plants. The systems biology of plant single-cell-types and single-cells requires the development of new methodologies to collect biological information and new computational tools to enhance the integration of these data sets. The establishment of advanced strategies to isolate and identify distinct cells comprising the plant is needed to reveal cellular heterogeneity, cell–cell communication, and signaling networks in plant biology. The comparative analysis of plants at the level of the single-cell will enhance interspecies comparisons by avoiding complications due to variation in tissue or organ anatomy. Many plant mutants have been characterized based on developmental and physiological defects. The biology of single-cell-types or single-cell systems applied to mutant plant cells should reveal molecular networks controlling cell-specific physiological and developmental processes in plants. Our understanding of plant biology is increasingly being built upon studies using ‘omics and system biology approaches performed at the level of the entire plant, organ, or tissue. Although these approaches open new avenues to better understand plant biology, they suffer from the cellular complexity of the analyzed sample. Recent methodological advances now allow plant scientists to overcome this limitation and enable biological analyses of single-cells or single-cell-types. Coupled with the development of bioinformatics and functional genomics resources, these studies provide opportunities for high-resolution systems analyses of plant phenomena. In this review, we describe the recent advances, current challenges, and future directions in exploring the biology of single-cells and single-cell-types to enhance our understanding of plant biology as a system. Our understanding of plant biology is increasingly being built upon studies using ‘omics and system biology approaches performed at the level of the entire plant, organ, or tissue. Although these approaches open new avenues to better understand plant biology, they suffer from the cellular complexity of the analyzed sample. Recent methodological advances now allow plant scientists to overcome this limitation and enable biological analyses of single-cells or single-cell-types. Coupled with the development of bioinformatics and functional genomics resources, these studies provide opportunities for high-resolution systems analyses of plant phenomena. In this review, we describe the recent advances, current challenges, and future directions in exploring the biology of single-cells and single-cell-types to enhance our understanding of plant biology as a system. analysis of the structure of genomes from multiple species, in terms of gene order, function, and orientation in the genome. Comparative genomic approaches have benefited from the recent release of numerous genomic resources notable in plant science. the collection of a class of molecules or biochemical characteristics from a single-cell, specific cell-type, tissue, organ, or whole organism. ‘Omic information varies depending on the type of biological data collected (e.g., epigenomic, transcriptomic, proteomic, or metabolomics data sets). one plant cell that has unique characteristics compared with its neighboring cells based on its developmental stage, unique response to environmental stresses, molecular heterogeneity, and so on. a collection of plant cells that have common physiological, anatomical, and/or functional characteristics. As a consequence, plant single-cells that belong to the same cell-type are also expected to share similar molecular and biochemical components. a field that seeks to understand complex biological processes through the integration of data sets (molecular, biochemical, etc.) at the level of a defined system (i.e., plant organelle, cell, tissue, organ, organisms, ecological communities, etc.).