The use of the Monoclonal Antibodies (MoAbs) Bevacizumab (B) and Trastuzumab (T) beyond clinical progression in colorectal and breast cancer treatment is among the hottest topics in today's clinical oncology. Both observational and prospective studies, based on a sound preclinical basis, seem to support the notion that, simply replacing the cytotoxic drugs combined with the two MoAbs would provide an additional clinical benefit without stopping the biological agent. The aim of this review is to provide a critical analysis of the available clinical data, while waiting for the confirmatory prospective clinical trials still ongoing. The strength and the weakness of this innovative strategy, as well as the associated expense and toxicity issues will be discussed.