Many of the cytotoxic drugs used in the treatment of non-small-cell lung carcinoma patients can interfere with DNA activity and the definition of an individual DNA repair profile could be a key strategy to achieve better response to chemotherapeutic treatment. Although DNA repair mechanisms are important factors in the prevention of carcinogenesis, these molecular pathways are also involved in therapy response. RAD51 is a crucial element in DNA repair by homologous recombination and has been shown to interfere with the prognosis of patients treated with chemoradiotherapy. There is increasing evidence that genetic polymorphisms in repair enzymes can influence DNA repair capacity and, consequently, affect chemotherapy efficacy. We conducted this review to show the possible influence of the RAD51 genetic variants in damage repair capacity and treatment response in non-small-cell lung carcinoma patients.