Therapeutic monoclonal antibodies are produced as secreted complex glycoproteins from mammalian cell systems and represent one of the most important classes of therapeutic medicines for multiple areas of treatment, including cancer, rheumatoid arthritis, and autoimmune diseases. The variations in glycosylation profile of recombinant monoclonal antibodies (rMAbs) have been shown to affect protein structure and stability, biological activity, and clinical efficacy through their mechanism of action, immunogenicity, and clearance rate. Although still considered a challenging task, attempts have been made in controlling glycosylation, for the production of a consistent glycan profile (homogeneous antibody glycoforms) in order to optimize therapeutic efficacy for a given disease state, including: enzymatic modifications of recombinant IgGs, cell engineering, and controlling culture conditions. This review aims to summarize present methods and strategies in manipulating protein glycosylation in rMAb production, and its importance for therapeutic applications. In addition, a better understanding of the glycosylation pathway will allow the prediction of resultant glycan profiles and facilitate the production of selected glycoforms.