 Anti-cancer drug resistance is a complex process that arises from altering drug targets and advances in DNA microarray, proteomics technology, and targeted therapies provide new strategies to overcome it. Although the design of new chemotherapy agents is growing quickly, effective chemotherapy agents have not been discovered against advanced stage cancer such as invasion and metastasis. The cancer cell resistance against anti-cancer agents can be due to various factors including genetic differences, drug mechanisms, multi-drug resistance, apoptosis suppression, altered drug metabolism, epigenetic changes, and drug targets. Treatment failures by common chemotherapy agents in different types of cancers are discussed in the review. This article was authored by Bezod Mansuri, Ali Mohamedi, Sadaf Davudian, and others.