The central nervous system is not a static, hard-wired organ. Examples of neuroplasticity, whether at the level of the synapse, the cell, or within and between circuits, can be found during development, throughout the progression of disease, or after injury. One essential component of the molecular, anatomical, and functional changes associated with neuroplasticity is the spinal interneuron (SpIN). Here, we draw on recent multidisciplinary studies to identify and interrogate subsets of SpINs and their roles in locomotor and respiratory circuits. We highlight some of the recent progress that elucidates the importance of SpINs in circuits affected by spinal cord injury (SCI), especially those within respiratory networks; we also discuss potential ways that spinal neuroplasticity can be therapeutically harnessed for recovery. SpINs are key cellular elements for plasticity following SCI. Advances in molecular genetics are allowing scientists to characterize populations of SpINs, integrated with motor and sensory functions. As SpIN subtypes are identified, their contribution to neuronal networks in the normal and injured spinal cord, and their role in plasticity can explored. Understanding how specific SpINs contribute to adaptive or maladaptive plasticity will enable the development of more targeted treatments for SCI. There is increased scientific and clinical interest in the contribution of SpINs to respiratory function following SCI (i.e., cervical) or disease (i.e., amyotrophic lateral sclerosis). The present review highlights some of these concepts, drawing on recent examples from locomotor and respiratory networks.