Colorectal cancer is one of the most common malignancies worldwide and is associated with high mortality rates. One of the classifications of colorectal cancer is based on the location of the primary tumor, distinguishing between left-sided and right-sided colorectal cancer. The different positions of the cancer result in variations in tumor development processes and molecular characteristics, leading to distinct clinical presentations of the disease and different responses to pharmacotherapy. Although not the gold standard, pharmacotherapy plays a crucial role in the treatment of colorectal cancer. It is used to reduce tumor mass before surgical intervention, decrease the risk of disease recurrence, improve the patient's quality of life, or when it’s the only treatment option left. Pharmacotherapy for colorectal cancer includes conventional chemotherapeutics, targeted therapy, and immune checkpoint inhibitors. Since different pharmacotherapeutic responses have been observed with certain drugs, the choice of appropriate pharmacotherapy partially depends on whether it is left-sided or right-sided colorectal cancer. The pharmacotherapy that shows the most significant difference in response depending on the tumor location is directed towards EGFR and VEGF. Considering these differences, it is essential to take into account the tumor's position when establishing a diagnosis to ensure optimal therapy for the patient.