In antiretroviral therapy Integrase Inhibitors (INIs) have become a key component since the approval of raltegravir in 2007 followed by the recent approval of elvitegravir in 2012. The next generation compound dolutegravir has obtained the approval from USFDA in August 2013. Dolutegravir possesses distinct characteristics like prolonged half-life, once-daily dosing without the need for any booster along with no significant effect of food on its pharmacokinetics. Earlier reports have shown that H51Y and R263K define a unique resistance pathway for dolutegravir. Dolutegravir is effective in both initial therapy and in the salvage of many patients who display resistance to both raltegravir and elvitegravir. Furthermore, due to its favorable metabolic profile and, without any dose adjustment, it can be co-administered with most of the other approved antiretroviral agents. These characteristics of dolutegravir along with reports from various ongoing phase III trials showed that it can be a promising investigational drug for future clinical uses. This review focuses on recent data of dolutegravir from well-designed clinical trials, resistance, with comparative drug interaction of various INIs.