Cancer has been one of the most prevalent causes of death around the world and despite the development of new therapeutic methods, traditional treatments including chemo and radiotherapy are still the pillars of cancer treatment. However, serious side effects and invasiveness limit the application of traditional cancer methods. To reduce the debilitating side effects of chemotherapy agents, targeted delivery of drugs to malignant cells has been the focus of much research in several past decades. Such efforts however have to overcome serious obstacles. Targeted delivery strategies have been applied to a wide range of cargos including nucleic acid base therapeutic molecules, peptides, and proteins as well as small molecule drugs. Recently, Cell Penetrating Peptides (CPPs) have been indicated as ideal transporters due to their desirable transitional features. CPPs are small synthetic or organic vehicles with the ability to form covalent or non-covalent bonds with a wide variety of substances. The capability of CPPs in crossing cell membranes, has received well-deserved attention in designing novel diagnoses and therapeutic strategies. In this review article, we compared structurally similar carriers designed by different research groups and discussed their strengths and limitations. The comparison was mainly based on the sequence properties of CPPs. We further discussed CPPs according to their cargo and reviewed their application in “in vivo” research. Research shows that despite the significant progress, drug delivery by CPPs has to address several issues, and such challenges have paved the way for further studies in the CPP field. Manuscript profile