HIV-1 infection is a major public health problem and an important cause of death among adults. In light of innate immune system being the first, rapid and nonspecific response, this highlights the importance of exploiting the active arms of innate immunity to eradicate the invader and triggering a more specific immune response, the adaptive immune system. Each type of cells in the innate immune system has a unique distribution and function in the body and therefore differs in their ability to induce adaptive immune arms according to the stimuli. Any functional defect or alteration in the innate immune system can affect the adaptive arms of the immune system in terms of failure to overcome the battlefield with the invader. This review focuses on the relevant function of each member of the innate immune system and sheds the light on detailed mechanisms about how this smart virus invades and evades the immune system which opens new insights into the immunology and therapeutic targeting of HIV-1 infection.