Carcinogenesis is a multistep process exhibiting deregulation in multiple cellular signaling pathways. Therefore, specific agent based treatments that target only one pathway usually fail in cancer therapy. The combination treatments using chemotherapeutic agents with distinct molecular mechanisms are considered more promising for higher efficacy; however, using multiple agents contributes to added toxicity. However, the in-vitro and in-vivo studies in the last few decades have demonstrated that some phytochemicals derived from ‘natural products’ such as fruits, vegetables and certain spices, referred to as chemopreventive agents, including capsaicin, trans-anethole, thymoquinone, diosgenin, allicin, can not only reduce the risk of acquiring specific cancer but also have been shown to suppress cancer cell proliferation, inhibit growth factor signaling pathways, induce apoptosis, inhibit nuclear factor-κB, AP-1, Akt, MAPK, Wnt, Notch, p53, AR, ER, and JAK-STAT, etc., activation pathways, inhibit angiogenesis, suppress the expression of antiapoptotic proteins, and inhibit cyclooxygenase-2. This study describes the above active components of some of the major spices, their mechanisms of action and their potential in prevention of various cancers.