Recently, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was quickly identified as the causal pathogen leading to the outbreak of SARS-like illness all over the world. As the SARS-CoV-2 infection pandemic proceeds, many efforts are being dedicated to the development of diverse treatment strategies. Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells, and nucleocytoplasmic trafficking inhibitor. To date, several direct anti-SARS-CoV-2 agents have demonstrated promising in vitro and clinical efficacy. This article reviews the current and future development of direct acting agents against SARS-CoV-2.