The term 'transgender' refers to a person has a different gender identity than the gender he/she/they was assigned to at birth. For example: a person was considered male at birth but feels like a woman. Gender dysphoria is a condition that is also characterized by an incongruence between a person’s experienced and assigned gender, but this term implies that the person suffers as a result of it. Studies estimate that in between 0.5% to 1% of the population identify as transgender, a percentage that has increased over the past years. Not all transgender people want, feel the need to appeal to, or have access to health care that helps them to physically transition into the gender they experience to be. However, in those who do, different drugs and protocols can be used. In children and adolescents, a different protocol is applied because their bodies are still evolving. Transgender adolescents often suffer more when their bodies start to change due to puberty and their bodies develop characteristics of a gender they do not feel related to. This is why puberty blockers can be used, because they halt puberty, thus relieving the suffering of the transgender adolescent. Puberty blockers also give them more time to explore their gender identity and make it easier to later transition into their experienced gender, should they want that. From the age of 15 years onwards, and when a team of health care professionals has agreed that the adolescent is mature enough to make this decision, gender-affirming hormonal therapy (i.e. treating the adolescent with sex hormones or the experienced gender) can be initiated. In children and adolescents, research on the efficacy and safety of these two categories of hormonal treatments is relatively sparse. This systematic review aims to give an overview of what is already known on this topic and to identify gaps in our knowledge. This is important, as it can help health care providers to choose which protocol is better for which patient, assists patients to make more informed choices and contributes to a better understanding of the risks and benefits of gender-affirming care. Hormonal treatment in children and adolescents with gender dysphoria is a polarized topic, and both those in favor, as well as those opposed to it reference to scientific evidence to corroborate their claims. This systematic review therefore aims to shed light on what is already known on this topic. This systematic review focuses only on the physical effects of hormonal therapy, excluding psychological effects. Relevant scientific literature was reviewed and 33 articles were selected. This evidence suggests that puberty blockers have a negative impact on the future length of adolescents and on the maturation of bones, while gender-affirming hormonal therapy has a positive impact on these two parameters. Researchers disagree on the impact of hormonal therapy on BMI, but seem to agree that it is safe regarding other parameters important to the heart and blood vessel system, such as lipids and blood pressure. Hormonal therapy also seems to be effective when looking at sex hormones and secondary sex characteristics, but has side effects like acne, headaches, hot flushes, fatigue and emotionality. When looking at parameters that are important to the sugar metabolism, the liver and certain hormones, authors did not find alarming changes during hormonal therapy. Very few research has been conducted on the effect of hormonal therapy on the brain. Preliminary evidence seems to suggest that IQ does not change during hormonal therapy and that puberty blockers magnify the brain differences between sexes, thus making the brain of a transgender adolescent even more different from that of their experienced gender. All-in-all, relatively few studies have been conducted on the somatic effects of hormonal therapy on transgender adolescents. Further research is therefore needed in order to fully comprehend its impact, and establish its safety and efficacy.