Background: p53 is the most mutated protein in cancer and the reactivation of its inactive mutated form represents one possibility for antitumor therapy. Reactivation leads to the initiation of apoptosis followed by the suppression of the malignant phenotype. Prima-1 and its methylated form Prima-1Met (also called APR-246) are compounds capable of reactivating mutated p53. Both are low-molecular substances that have been tested in a number of tumor cell lines and tumors bearing mutated p53. Aim: This article summarizes what is currently known about both compounds, describes the possibilities of their use in anti-tumor therapy, and outlines the results of currently undergoing clinical trials of APR-246. Conclusion: The results show that the mechanism of action of both compounds is still not clear. The mechanism is only known clearly in the case of Prima-1, and APR-246 is only known to induce apoptosis. The specificity of both substances for mutated p53 differs considerably and depends mainly on the cell model employed and the type of mutation. In addition to p53 reactivation itself, these compounds likely influence other mechanisms that also affect cytotoxic activity.