Gemcitabine, an analog of deoxycytidine, is an anticancer nucleoside with proven activity in different solid malignancies. The efficacy of gemcitabine as a single agent or as part of a combination treatment has been evaluated in several trials, and antitumor activity has been observed in patients with sensitivity and resistance to both platinum and paclitaxel. In this context, preclinical studies have shown that gemcitabine-based combinations increase the cytotoxic action of the treatment and can potentially overcome drug resistance. The toxicity profile of gemcitabine, and its proven action in relapsed ovarian cancer, allows for the development of a hypothesis stating that a specific choice of drugs with different mechanisms and non-cross-resistance can increase the chance of response and prolong its duration and that of other outcome measures. This article provides an update of new clinical approaches with gemcitabine in combination with other nonplatinum drugs for the management of patients with platinum-resistant ovarian cancer.