The attractive features of lanthanide-doped upconversion luminescence (UCL), such as high photostability, nonphotobleaching or photoblinking, and large anti-Stokes shift, have shown great potentials in life science, information technology, and energy materials. Therefore, UCL modulation is highly demanded toward expected emission wavelength, lifetime, and relative intensity in order to satisfy stringent requirements raised from a wide variety of areas. Unfortunately, the majority of efforts have been devoted to either simple codoping of multiple activators or variation of hosts, while very little attention has been paid to the critical role that sensitizers have been playing. In fact, different sensitizers possess different excitation wavelengths and different energy transfer pathways (to different activators), which will lead to different UCL features. Thus, rational design of sensitizers shall provide extra opportunities for UCL tuning, particularly from the excitation side. In this review, we specifically focus on advances in sensitizers, including the current status, working mechanisms, design principles, as well as future challenges and endeavor directions.