Great progress has been made in the past several decades concerning C-H bond functionalization. But despite many significant advances, a commercially viable large-scale process for selective alkane functionalization remains an unreached goal. Such conversions will require highly active, selective, and long-lived catalysts. In addition, essentially complete atom-economy will be required. Thus, any reagents used in transforming the alkanes must be almost free (e.g., O2, H2O, N2), or they should be incorporated into the desired large-scale product. Any side-products should be completely benign or have value as fuels (e.g., H2 or other alkanes). Progress and promising leads toward the development of such systems involving primarily molecular transition metal catalysts are described.