Doxorubicin is a chemotherapeutic agent that inhibits topoisomerase II, intercalates within DNA base pairs and results in oxidative DNA damage, thus inducing cell apoptosis. Although it is effective in the treatment of a wide range of human cancers, the emergence of resistance to this drug can increase tumour growth and impact patients' survival. Numerous molecular mechanisms and signalling pathways have been identified that induce resistance to doxorubicin via stimulation of cell proliferation, cell cycle switch and preclusion of apoptosis. A number of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have also been identified that alter sensitivity to doxorubicin. Understanding the particular impact of these non-coding RNAs in conferring resistance to doxorubicin has considerable potential to improve selection of chemotherapeutic regimens for cancer patients. Moreover, modulation of expression of these transcripts is a putative strategy for combating resistance. In the current paper, the influence of miRNAs and lncRNAs in the modification of resistance to doxorubicin is discussed.