Two-dimensional (2-D) electrophoresis remains the highest resolution technique for protein separation and is the method of choice when complex samples need to be arrayed for characterisation, as in proteomics. However, in current proteome projects the total number of proteins identified from 2-D gels is often only a small percentage of the predicted proteome. In addition, there is an almost complete lack of hydrophobic proteins on 2-D gels, especially those using immobilised pH gradients. Recently there have been a number of publications reporting reagents which improve protein solubilisation prior to isoelectric focusing. The improved solubilization possible with these reagents has increased the total number of proteins able to be visualised on 2-D gels and also allowed the separation of hydrophobic proteins, such as integral membrane proteins.