The HIV epidemic has shed light on how government regulation of sex work directly affects the health and well-being of sex workers, their families and communities. A review of the public health evidence highlights the need for supportive legal and policy environments, yet criminalisation of sex work remains standard around the world. Emerging evidence, coupled with evolving political ideologies, is increasingly shaping legal environments that promote the rights and health of sex workers but even as new legislation is created, contradictions often exist with standing problematic legislation. As a region, Asia provides a compelling example in that progressive HIV policies often sit side by side with laws that criminalise sex work. Data from the 21 Asian countries reporting under the UN General Assembly Special Session on HIV in 2010 were analysed to provide evidence of how countries' approach to sex-work regulation might affect HIV-related outcomes. Attention to the links between law and HIV-related outcomes can aid governments to meet their international obligations and ensure appropriate legal environments that cultivate the safe and healthy development and expression of sexuality, ensure access to HIV and other related services and promote and protect human rights.