Twin pregnancies present unique and multifaceted challenges for prenatal testing due to their overall increased risk of chromosomal and structural anomalies compared to singleton pregnancies. Both invasive and noninvasive methods play important roles in risk assessment, diagnosis, and management of these higher-risk pregnancies. Noninvasive approaches for screening of aneuploidies, such as first-trimester combined screening and cell-free DNA (cfDNA) testing, have demonstrated comparable efficacy to those in singleton pregnancies when adjustments for chorionicity are made. cfDNA testing offers the highest detection rate and lowest false-positive rate for screening of trisomy 21, although it presents unique challenges in twin pregnancies. In cases where noninvasive testing shows a high risk for aneuploidies, invasive procedures such as chorionic villus sampling or amniocentesis are necessary for definitive diagnosis. These procedures, however, require specialized expertise due to technical challenges and the potential for procedure-related complications, including fetal loss. This chapter explores the full spectrum of testing strategies, emphasizing individualized care based on chorionicity, accurate risk assessment, and advancements in prenatal diagnostic technology to optimize maternal and fetal outcomes.