The question of whether activated microglial cells are potentially harmful or beneficial to injured central nervous system neurons is being addressed by examining in vivo and in vitro findings. While observations made in vivo suggest that microglial activation is triggered by injured neurons and may aid in regeneration, in vitro data show production of neurotoxic agents by cultured microglia. An effort is made to find a common denominator in these apparently conflicting findings by discussing microglial activation during motor neuron regeneration and during delayed neuronal death occurring as a consequence of global forebrain ischemia.