The number of human immunodeficiency virus (HIV) cases in Afghanistan is increasing mainly associated with injecting drug use (IDU). This study aimed to explore the risk and vulnerability factors associated with HIV infection among injecting drug users (IDUs) in Afghanistan in order to contribute to improving the response and reversing the concentrated HIV epidemic among this group. A narrative review of the literature was conducted to reach the objective. The modified social ecological model was used as conceptual framework for analysis of the HIV risk and vulnerability factors among IDUs at five levels. At the "individual level", the injecting risk behaviors among IDUs such as sharing the injecting equipment and their sexual risk behaviors like unprotected sexual contact with multiple partners identified as immediate factors that put them at risk of HIV infection. At the "network level", lack of HIV knowledge and low uptake of the harm reduction services were identified as the factors that increase their vulnerability. At the "community level", massive drug production and easy access to illicit drugs, armed conflicts, massive internal and external migration, unemployment and poverty, high stigma and discrimination against IDUs, unsafe injecting locations such as under the bridges; and at the "public policy level", punitive drug laws, and weak national political response to HIV and IDU were identified as determinants that add to the IDUs vulnerability to HIV. At the "stage of epidemic level", the concentrated HIV epidemic among IDUs in the country poses a potential risk to uninfected IDUs and beyond. In conclusion, the IDUs in Afghanistan are highly at risk and vulnerable to HIV. An informed and multisectoral response is required to control the epidemic. A rapid expansion of the harm reduction interventions is urgently needed.