99mTc radiopharmaceuticals play an important role in widespread applications of nuclear medicine. When 99mTc radiopharmaceuticals first came into use, major efforts were directed toward the development of 99mTc radiopharmaceuticals for bone imaging and for the excretory functions of the liver and kidneys. In the past 20 years, a significant advance has been made in technetium chemistry, which provided 99mTc radiopharmaceuticals for assessment of regional cerebral and myocardial blood flow. Recent efforts have been directed toward the design of 99mTc-labeled compounds for estimating receptor or transporter functions. A number of bifunctional chelating agents that provide 99mTc labeled proteins and peptides of high in vivo stability with high radiochemical yields have also been developed. More recently, organometallic technetium and rhenium compounds have been introduced as another class of 99mTc radiopharmaceutical design. In this manuscript, recent progress in 99mTc radiopharmaceuticals is reviewed with the major emphasis laid on key innovations in this field to provide the 99mTc radiopharmaceuticals available today.