IntroductionThe offer of pre‐exposure prophylaxis (PrEP) is recommended as an additional option for HIV prevention for people at substantial risk of HIV infection as part of combination HIV prevention approaches. Implementing this depends on integrating PrEP in public health programmes that address risky practices with evidence‐based interventions, and that operate in an enabling legal and policy environment for the delivery of health services to those at higher risk of HIV infection. What does this recommendation mean in terms of the diverse range of HIV prevention needs of key populations, some of whom are so discriminated against that they exist essentially outside formal systems such as national public health services, and for whom a substantial risk of HIV is part of a larger adverse and hostile situation? We discuss this question with reference to people who inject drugs, informed by concerns and comments that emerged from a series of consultations.DiscussionHIV prevention is part of a spectrum of injecting drug users’ priorities, and their access and uptake of HIV prevention services is contingent on their wider “risk environment.” The need to address structural barriers to services and human rights violations, and to improve access to comprehensive harm reduction programmes are of prime importance and would have higher value than a mono‐focus on HIV prevention. Where existing harm reduction activities are inadequate, fragile or dependent on external donors, shifts in funding priorities, including, for example, towards PrEP, could threaten investment in the broader programmes. For these reasons, it cannot be assumed that PrEP promotion will always be supported by people who inject drugs.The sexual partners of people who inject drugs, non‐opioid users who also inject and for whom there is no established substitution treatment, as well as drug users who are unable to negotiate safe sex may value PrEP. As for all key populations, the involvement of people who inject drugs in shaping services for their consumption is vital and too often ignored.ConclusionsFor people who inject drugs and who experience discrimination, violence or harassment, implementation of PrEP should be guided by understanding and engaging with their interconnected range of needs, risk practices, priorities and options. The differentiated needs of sub‐populations that inject a range of drugs, and their sexual partners, require further exploration.