Rho kinase (ROCK) belongs to a family of serine/threonine kinases that are activated via interaction with Rho GTPases. ROCK is involved in a wide range of fundamental cellular functions, such as contraction, adhesion, migration, and proliferation. Recent studies have shown that ROCK plays an important role in the regulation of apoptosis in various cell types and animal disease models. Two ROCK isoforms, ROCK1 and ROCK2, are assumed to be function redundant, this based largely on kinase construct overexpression and chemical inhibitors (Y27632 and fasudil) which inhibit both ROCK1 and ROCK2. Gene targeting and RNA interference approaches allow further dissection of distinct cellular, physiological, and patho-physiological functions of the two ROCK isoforms. This review, based on recent molecular, cellular, and animal studies, focuses on the current understanding of ROCK signaling in the regulation of apoptosis and highlights new findings from recently generated ROCK-deficient mice.