Despite the vast advances, cancer therapy still presents several challenges, especially related to the low efficacy and specificity of antitumor drugs. In this regard, the organoselenium compounds emerge as a promising alternative to overcome these problems. These compounds are reported to have chemopreventive and antitumor activity, inducing apoptosis and preventing metastasis. These activities have been evaluated in different tumor cells as monotherapy or associated with other antitumor drugs and radiation. In this context, this chapter provides an insight into organoselenium compounds with potential antitumor activity, and discusses their applications, current limitations, and future perspectives. It also highlights the application of nanocarriers as a technological strategy to enhance the antitumor potential of these promising compounds.