Aging and life span are widely recognized, but poorly understood, aspects of basic biology. Fortunately, genetic approaches to understanding the mechanisms governing these processes are beginning to bear fruit. One line of investigation has established that incompletely reduced forms of oxygen, arising as by-products of respiration and cellular catabolism, play an important, and perhaps universal, role in aging and life span determination. An important refinement of this model of aging, suggested by recent experiments in our laboratory, is that the critical nexus of the relationship between reactive oxygen species and life span is highly localized and, in fact, may reside principally in the motorneuron. Here we analyze the strengths and weaknesses of the reactive oxygen species/motorneuron model of aging by comparing the studies on which it is based, which used the approach of targeted transgene expression in Drosophila, with studies from other laboratories using different genetic approaches, principally mutation and selection. The results encourage the view that an understanding of the mechanisms that underlie this widely recognized aspect of basic biology is within our grasp.