In terms of regulation, the PI3K inhibitor medication class had a difficult 2022. Participants in a historic FDA advisory committee meeting in April were warned about dubious safety and efficacy. Less than three months later, the FDA issued a duvelisib (Copiktra) safety warning about mortality rates. As a result, the FDA’s Oncologic Drugs Advisory Committee (ODAC) decided against recommending duvelisib’s approval for the treatment of chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL). Along the way, the FDA also voluntarily withdrew or revoked a number of PI3K inhibitors’ approved indications. Does the medication class have a promising future in the treatment of hematologic malignancies in light of this negative energy?