These guidelines aim to inform the design and implementation of interventions with young key populations (YKP), 15-24 years, specifically young women who sell sex, young men who have sex with men, and young people who inject drugs. The guidelines aim to accelerate the HIV response to end new HIV infections among young key populations. They highlight that YKP experience more unprotected sex, sexually transmitted infections including HIV, unintended pregnancy, violence, mental health disorders, and substance use compared to older/mature members of key populations and youth among the general population. YKP experience significant barriers to accessing care; coverage of services is low, largely because of stigma and discrimination experienced at both the health system and policy levels. The need to work with young key populations who are generally hard to reach and are missed by programmes meant for young people or for adult key populations is highlighted. The guidelines recommend evidence informed combination prevention approaches and defines specific interventions including research that are expected to accelerate achievement of the goal when implemented at scale. They also emphasize the need to involve young key populations at all levels of programme and policy design, implementation, and evaluation. A monitoring and evaluation plan is also drawn out which builds on existing systems and mechanism of data collection and analysis. A programme science approach addresses specific knowledge gaps and recommends a continuous effort to assess the approaches of programming, their successes, and challenges.