In the year 1979, esteemed Dr. P.J. Mehta published the First edition of “Practical Medicine for Students and Practitioners”. The book has stood the test of time through over nearly 40 years and 20 earlier editions.It is with great pride that we present the twenty-first edition of P.J. Mehta’s Practical Medicine. We would like to acknowledge the guidance and contribution of the earlier editors of the book. Keeping up with the constant advances in the field of medicine, this edition has many changes. This book still emphasizes the importance of analysis of symptoms and signs and formation of a differential diagnosis before going on to interpretation of various investigations.