Microglial cells are exquisitely sensitive to neuronal damage. Neurons which have been damaged by an injury or a neurotoxicant will stimulate microglia in their immediate vicinity to become activated and undergo a series of morphologic and phenotypic changes. The changes occurring on microglial cells can be documented quite readily using histochemical methods, and it is suggested that the histological demonstration of microglial activation can serve as a very sensitive biological marker for neuron damage. While the functional significance of microglial activation is unknown, there is evidence to suggest that microglia may exert both neurotrophic and neurotoxic effects. However, proving that these functions are indeed carried out by microglia in vivo remains a formidable challenge for future investigations.