Bilevel Optimization is an extremely powerful tool for modeling realistic problems in multiple areas. On the other hand, Bilevel Optimization is known to frequently lead to complex or intractable problems. In this thesis, we present three works expanding the state of the art of bilevel optimization and its intersection with power systems. First, we present BilevelJuMP, a novel open-source package for bilevel optimization in the Julia language. The package is an extension of the JuMP mathematical programming modeling language, is very general, feature-complete, and presents unique functionality, such as the modeling of lower-level cone programs. The software enables users to model a variety of bilevel problems and solve them with advanced techniques. As a consequence, it makes bilevel optimization widely accessible to a much broader public. In the following two works, we develop specialized methods to handle much model complex and very large-scale bilevel programs arising from power systems applications. Second, we use bilevel programming as the foundation to develop Application-Driven Learning, a new closed-loop framework in which the processes of forecasting and decision-making are merged and co-optimized. We describe the model mathematically as a bilevel program, prove convergence results and describe exact and tailor-made heuristic solution methods to handle very large-scale systems. The method is applied to demand forecast and reserve allocation in power systems operation. Case studies show very promising results with good quality solutions on realistic systems with thousands of buses. Third, we propose a simulator to model long-term bid-based hydro-thermal power markets. A multi-stage stochastic program is formulated to accommodate the dynamics inherent to hydropower systems. However, the subproblems of each stage are bilevel programs in order to model strategic agents. The simulator is scalable in terms of system data, agents, scenarios, and stages being considered. We conclude the third work with large-scale simulations with realistic data from the Brazilian power system with 3 price maker agents, 1000 scenarios, and 60 monthly stages. These three works show that although bilevel optimization is an extremely challenging class of NP-hard problems, it is possible to develop effective algorithms that lead to good-quality solutions.