Therapeutics proteins require protection against several sources of chemical and /or physical instabilities. One such physical instability is the high tendency of protein molecules to aggregate under a wide range of processing and storage conditions. Aggregates of the protein drug may enhance the product's immunogenicity and could compromise its efficacy. There are two major pathways of protein aggregation; these are aggregation of native protein conformations (colloidal instability) or aggregation of partially denatured proteins (non-native protein aggregation). Certain solution conditions, which reduce aggregation through one pathway, may lead to an increase in aggregation through the other pathway; therefore, a logical balanced formulation procedure should be implemented in order to reduce aggregation due to both pathways. For certain protein molecules, optimizing solution conditions might not result in the required reduction in protein aggregation; in this case, alteration in the protein structure might be required. This alteration can be, either in vivo through protein coding gene manipulation or synthetic such as protein PEGylation. There are two aggregation pathways for protein in liquid formulations, aggregation due to conformational stability and aggregation due to colloidal instability. Protein melting temperature (Tm) and time-dependent rate of thermal unfolding can assess conformational stability of a protein while measurement of second virial coefficients from static light scattering or protein precipitation in the presence of a salting out salt such as ammonium sulphate can be used to assess colloidal stability of a protein.