Transgender individuals assigned female at birth (t-AFAB) seek gender-affirming care to align their physical characteristics with their gender identity, which can include hormone treatment and/or surgical treatments. Testosterone treatment is the cornerstone: its aim is to alleviate gender dysphoria by reducing incongruence between body phenotype and gender identity, while improving overall psychological well-being. Testosterone therapy induces a broad spectrum of physical changes that gradually masculinize the phenotype: menstrual suppression, changes in body composition and fat distribution, increases in muscle mass and strength, growth of facial and body hair, clitoral enlargement, deepening of the voice, and alterations in skin texture. Although amenorrhea and ovulatory suppression typically occur, fertility preservation should be discussed before initiating hormone treatment. Ovulation and conception may still rarely occur; thus, testosterone should not be considered a reliable contraceptive, and individualized contraceptive counseling is essential during follow-up. Testosterone therapy is generally safe and effective, though potential adverse effects may include erythrocytosis, but rarely clinically relevant, acne, androgenetic alopecia, atherogenic alterations in lipid metabolism. Evaluation of bone health, including risk factors for fragility fractures and treatment adherence, is recommended. Concerns have also been raised about oncological risks: primarily cervical and breast cancer. Tailored screening protocols, according to the individual’s anatomy, should be ensured.