Since its introduction, digital breast tomosynthesis (DBT) has been widely incorporated in screening for breast cancer due to its lesser recall and higher cancer detection rates. Some screen-detected lesions may be visible only by DBT, requiring biopsy using DBT guidance. This review article dissects the different steps of tomosynthesis-guided biopsy and discusses the different obstacles that might be encountered during each step while providing the appropriate solutions, hence allowing physicians to perform a successful biopsy with the least patient discomfort.