With the need followed by success of organ transplantation, use of immunosuppressive drugs has become a necessity. Cyclosporine, one of the commonly used immunosuppressive drug has an undesirable side effect of gingival overgrowth. Whereas gingival overgrowth is an infrequent side effect with Tacrolimus, a potent immunosuppressive drug, when compared to Cyclosporine. Eventhough several hypothesis have been put forward, the exact mechanism underlying this untoward effect is not fully understood. This book attempts to review all the pathogenic mechanism in general and also discuss an experimental study done on wister rats comparing collagen content, MMP1, MMP2 and TIMP1 in Cyclosporine and Tacrolimus induced gingival overgrowth. This book will provide insight to researchers about the influence of drugs on connective tissue metabolism.