The techniques used in anticancer drug discovery research have evolved tremendously since the first anticancer drug was discovered in the 1950s. The rise of the omics era in the 1990s, especially in genomics and proteomics, has revealed many potential new anticancer drug targets. Recent advancements in technology and computational power have increased the popularity of in silico and biophysical techniques in drug discovery campaigns among academicians and industry players, including the cancer research communities. In this chapter, we introduce some of the commonly used in silico and biophysical techniques in the discovery of anticancer drugs that the FDA has approved. This chapter also illustrates some real-life examples of successful integration of in silico and biophysical techniques in anticancer drug discovery. The future perspective of anticancer drug discovery research is also discussed.