The assertion that efficacy of “targeted therapies” (TAR) cannot be assessed by traditional response measures has become conventional wisdom often guiding trial design and interpretation. Because stable disease (SD) has been increasingly reported as a measure of activity even for “cytotoxic therapies” (CTX), we sought to compare the occurrence of SD in phase II trials of cytotoxic CTX and TAR. We catalogued response assessments in 143 phase II studies reported in 5 journals between October 2006 and March 2008. Eighty-five studies incorporated CTX and 58 administered TAR. Both groups had comparable distribution of histologies and similar progression free survival (PFS) (median 4.8/2.35 months) and OS (median 10.9/9.15 months). SD was defined in only 28.6% of studies (median 10 weeks). SD rates were nearly identical—mean/median 35.05/34.7% for CTX, and 32.3/31.05% for TAR—with similar distributions across histologies, suggesting SD may not reflect drug activity. There were no positive correlations between %SD and PFS or OS. The overall response rate (complete response + partial response) was higher with CTX therapies (mean/median, 28/25% versus 13.1/5.3%) and in both groups overall response rate demonstrated a strong correlation (P < 0.0001) with PFS and OS. As currently defined and measured SD is not a property of TAR but is as frequently found with CTX therapies and may not reflect antitumor activity. Responses are observed with “both classes” of therapy and should be sought as a measure of activity. Studies that use SD as an end point require an adequate control to distinguish antitumor activity from normal variability in time to progression.