This chapter reviews significant recent clinical trials involving potential disease-modifying drugs, including active immunotherapy, passive immunotherapy, γ-secretase inhibitors and modulators, β-secretase inhibitors, and amyloid-beta (Aβ) anti-aggregants. The challenges and opportunities involved in global trials are then discussed, such as variability in diagnosis and patient selection; patient endpoints for both symptomatic therapies and disease-modifying drugs; rater training and global validation of rating scales; competition to recruit the pool of patients available for clinical trials; and emerging logistical concerns related to the use of biomarkers.