Quantum simulation, a subdiscipline of quantum computation, can provide valuable insight into difficult quantum problems in physics or chemistry. Ultracold atoms in optical lattices represent an ideal platform for simulations of quantum many-body problems. Within this setting, quantum gas microscopes enable single atom observation and manipulation in large samples. Ultracold atom–based quantum simulators have already been used to probe quantum magnetism, to realize and detect topological quantum matter, and to study quantum systems with controlled long-range interactions. Experiments on many-body systems out of equilibrium have also provided results in regimes unavailable to the most advanced supercomputers. We review recent experimental progress in this field and comment on future directions.