The broad spectrum caspase inhibitor, Q-VD-OPh, provides not only a cost effective, non-toxic, and highly specific means of apoptotic inhibition but also new insight into next generation caspase inhibitors. Our data indicate that the specificity and effectiveness of next generation caspase inhibitors will be significantly enhanced by incorporating conjugated aminoterminal quinolyl and carboxyterminal O-phenoxy groups. A major disadvantage of fluoromethyl ketone and other carboxyterminal-conjugated caspase inhibitors has been the resultant toxicity in vivo which has hampered their use. Future studies examining other amino terminal modifications to 0-phenoxy conjugates to decrease hydrophobicity as well as nonpeptide, selective caspase inhibitors should provide even greater effectiveness. Studies assessing in vivo specificity, clearance, and toxicity of Q-VD-OPh will determine the potential use of this new generation of Ophenoxy caspase inhibitor conjugates as promising new therapeutics.