The Highly Improved Staggered Quark (HISQ) action is the next-generation improved action for calculations in lattice QCD that rely on the staggered fermions formalism. The dominant O(a2) discretization error in current simulations arises from the splitting of the continuum pion into several non-degenerate "tastes" at nonzero lattice spacing. The HISQ action significantly reduces the splitting among different pion tastes, thus providing faster approach to the continuum limit. In this talk I review simulations with dynamical highly improved staggered quarks (that pose some computational challenges) and present recent results for a set of ensembles with the light quark masses set to 1/5 of the strange quark mass and with the strange and charm quark masses tuned to their physical values. I also review an exploratory study of the QCD Thermodynamics with HISQ at almost physical light quark masses.