The statistical analysis of microbiome data presents unique challenges including high dimensionality, compositional constraints, sparsity, and phylogenetic structure that complicate conventional statistical approaches. This chapter outlines key steps for common microbiome analysis tasks including research question formulation, data preprocessing, descriptive analysis, statistical modeling, and validation for comparisons of diversity and differential abundance estimation. Specific methods are discussed, as well as general considerations for selecting methods and avoiding common statistical pitfalls in this rapidly evolving field.