The vision for North Temperate Lakes (NTL) LTER is to gain a predictive understanding of lakes and lake districts at longer and broader scales than has been traditional in limnology. We employ long-term observations, comparisons, experimental manipulations, and diverse modeling and statistical tools to understand change in social-ecological systems. Here, we highlight four ongoing initiatives that demonstrate our multifaceted, interdisciplinary approach to research. Biogeochemical and microbial consequences of unexpected changes in lake thermal structure are being studied by experimental lake mixing, and demonstrate strong directional changes in bacterial community composition and accelerated rates of respiration. Measuring metabolism is a core LTER mission. Comparative studies and modeling have been used to evaluate methods for estimate ecosystem production and respiration using high-frequency data, and have revealed that simplest models are often the best. Problems of eutrophication and water clarity have been long-standing in Madison’s Yahara Lake District. Along with several partners, we are examining the effects of a large-scale carp removal from Lake Wingra. Monitoring and comparison to the long-term LTER record reveal major increases in water clarity in the first two years of fish removal. Finally, these examples touch on some of the ecosystem services provided by lakes and lake districts. Ongoing efforts are focusing on the magnitude, interactions, and potential future flows of ecosystem services in NTL’s northern and southern lake districts.