Direct amidation of C–H bonds is a highly desirable reaction considering high utility of amidated products in total synthesis, medicinal chemistry and materials science. Although tremendous research efforts have been made especially in recent years, the current status enabling such C–H reactions in excellent stereoselectivity and high efficiency is still rather limited. In this context, we have developed a novel methodology that employs tailor-made Ir-based catalysts in combination with dioxazolone substrates to access a short-lived metal-nitrenoid intermediate, thereby eventually leading to a construction of γ-lactams via an outer-sphere C–H insertion pathway. The scope was found to be broad and a range of carboxylic acids could be readily utilized for the lactam formation. Indeed, the power of this new method was demonstrated in the successful late-stage functionalization of bio-active molecules to produce molecules that are highly sought after for pharmaceutical applications. More recently, we have successfully introduced an iridium-based catalyst system for asymmetric C−H amidation that enables facile construction of chiral γ-lactams starting from commodity chemicals. Various types of secondary C−H bonds, such as being positioned at the benzylic, unactivated aliphatic, propargylic, and allylic sites, were all smoothly reacted in a regio- and stereoselective manner. The present approach will find broad applications in medicinal chemistry, and the mechanistic insights may provoke further developments in related asymmetric catalysis.