Among the wide variety of food bioactives subjected to encapsulation, probiotics hold immense significance owing to their innumerable benefits to human gastrointestinal health. Encapsulation by spray drying provides a physiological barrier that protects these highly sensitive living entities during processing and storage. The objectives of this chapter are to define probiotics and to explain the rationale for probiotics encapsulation and optimization of spray drying parameters to completely achieve the functional benefits of probiotics. Probiotic characteristics and wall material properties of importance to encapsulation by spray drying are elaborated in this chapter. The influence of spray drying parameters on the viability of probiotic cells and the methods of increasing cell viability during spray drying process are also detailed here. A compilation of the commonly employed processing parameters for encapsulation of probiotic cells by spray drying are presented for the benefit of readers.