Image-guided percutaneous needle biopsy (PNB) is a safe and effective procedure used by interventional radiologists. This minimally invasive approach to biopsy offers high success and low adverse event rates, enabling definitive tissue diagnosis when characterization by imaging or laboratory testing is insufficient. While the basic techniques and principles of PNB are similar across organs, there are special considerations and approaches for different organs, including the liver, kidneys, adrenal glands, spleen, and pancreas. To optimize outcomes and safety profiles, pre-procedural workup, indications/contraindications, and patient selection strategies are important considerations. Adjunct procedures, including hydrodissection and gelfoam tract embolization, are available to enhance procedural efficacy and safety. This chapter provides a comprehensive review of image-guided percutaneous needle biopsies, highlighting their safety, effectiveness, and wide application across various deep organs, while emphasizing pre-procedural assessments, organ-specific biopsy techniques, adjunct procedures, periprocedural management, and potential adverse events.