Cello-oligosaccharides (COS) are small carbohydrate molecules derived from cellulose through partial hydrolysis. COS exert physiological influence on plants, animals and humans when externally dosed or consumed. Their potential as a prebiotic for humans and animals and as an elicitor for plants has generated interest in their synthesis and purification. Currently, their lack of availability, even at scales necessary for research, has restricted the progress in this field. In this review, we explore the methods for depolymerization of cellulose with a focus on catalytic partial hydrolysis to COS. Aspects of cellulose depolymerization using enzymes, homogeneous catalysts and heterogeneous catalysts are described. Methods for qualitative and quantitative characterization of COS are discussed along with future challenges in COS synthesis. Role of mechanocatalysis and other technologies in branched oligosaccharide synthesis is also explored for solvent free cellulose depolymerization.