Mitochondria are highly dynamic organelles that constantly change shape and structure in response to different stimuli and metabolic demands of the cell. Mitochondrial structure in the cell is predominantly regulated by cycles of fusion and fission. These two processes are tightly regulated and under physiological conditions, mitochondrial fusion is evenly counterbalanced by fission. During apoptosis, mitochondria undergo extensive fragmentation, which precedes caspase activation, whereas inhibition of the mitochondrial fission machinery blocks or delays cell death. Aberrant mitochondrial fusion and fission have also emerged as important mechanisms in the development of disease. In this chapter we will briefly discuss mechanisms of mitochondrial fusion and fission in mammalian cells, the mitochondrial morphogenesis proteins that may be involved in these processes and role of these processes in cell viability. This will be followed by a review of recent work connecting mitochondrial morphogenesis proteins with the progression of the mitochondrial steps in apoptosis, as well as stimulating findings showing that certain proteins associated with apoptosis regulation can also participate in the regulation ofmitochondrial fusion and fission in healthy cells.