Depression is a mood disorder that ranks fourth in terms of the frequency of illnesses worldwide. This condition is characterized by various psychological symptoms associated with low mood, negative self-perception, a negative view of the world, and a lack of motivation. There are various theories regarding the onset of this condition, but it is believed to be the result of multiple factors. The diagnosis of this disorder is based on criteria that must be met, relating to the quantity and duration of depressive symptoms. Treatment options include psychotherapy, pharmacotherapy, electroconvulsive therapy, and other methods such as lifestyle changes. Adequate treatment greatly enhances the fight against this illness. Depression often co-occurs with other chronic diseases, including malignancies. Malignant diseases themselves are unpredictable, causing fear and anxiety and having a profound impact on a person's mental state. Patients who simultaneously suffer from depression and malignancies have been proven to have a poorer response to treatment, prolonged hospital stays, and a worse prognosis for the malignant disease itself. The theory of depression onset in these patients is supported by various biological concepts, as well as the influence of stress itself. When treating these patients, caution must be exercised regarding possible interactions between antidepressants and other medications, as well as altered pharmacodynamics and pharmacokinetics. Psychotherapy plays an extremely important role as it helps patients adapt, cope with the illness, and manage the inevitable pain. A comprehensive approach to the patient is crucial in order to timely recognize the mental disorder and adequately address its treatment alongside the underlying disease.