Stille reaction is one of the most common, efficient and selective Pd-catalyzed cross-coupling reactions for the construction of C-C bonds in the art of organic synthesis. It was initially achieved and reported in 1978 b y J. K. Stille and D. Milstein. This reaction is based on organotin compounds in the presence of catalytic amount of Pd complexes which can be performed in mild reaction conditions. Nowadays, this strategy is considered as a powerful tool in the total synthesis of a wide variety of natural products and non-natural biologically active compounds as well as synthetic key intermediates in the curtail C-C bonds construction steps. In 2013 we reported the applications of Stille reaction in the total synthesis of natural products, published in Tetrahedron. Due to huge numbers of references regarding the applications of this name reaction in the total synthesis of naturally occurring compounds, we thought it is worthwhile to update our aforementioned reports, highlighting the applications of Stille coupling reaction in the total synthesis of biologically active natural products, including macrolides, alkaloids, cyclic ethers, terpenes and lactones accomplished between 2013 till date.