Active anticancer molecules have been searched from natural products; many drugs were developed from either natural products or their derivatives following the conventional pharmaceutical paradigm of drug discovery. However, the advances in the knowledge of cancer biology have led to personalized medicine using molecular-targeted agents which create new paradigm. Clinical benefit is dependent on individual biomarker and overall survival is prolonged through cytostatic rather than cytotoxic effects to cancer cell. Therefore, a different approach is needed from the single lead compound screening model based on cytotoxicity. In our experience, the Rhus verniciflua stoke (RVS) extract traditionally used for cancer treatment is beneficial to some advanced cancer patients though it is herbal extract not single compound, and low cytotoxic in vitro. The standardized RVS extract's action mechanisms as well as clinical outcomes are reviewed here. We hope that these preliminary results would stimulate different investigation in natural products from conventional chemicals.