Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disease. Despite significant research efforts, there is currently no general established disease-modifying therapy that can halt or reverse the progression of AD. A key challenge lies in the lack of relevant experimental models to effectively study disease progression. In recent years, complex stem cell-derived 3D brain models have emerged as promising new tools to study human brain development, brain aging, and neurodegeneration. These innovative models offer renewed hope for identifying disease-modifying therapies. However, significant challenges must be addressed before these 3D models can achieve broader application. This chapter provides an overview of the latest advancements in 3D brain in vitro models, their relevance in AD research, and their advantages and limitations.