End-of-life (EOL) conversations are difficult for patients, families, and health care providers. Strategies are needed to elicit seriously ill patients’ care preferences. Ongoing discussions between patients and health care providers, throughout the course of a serious disease, can increase patients’ self-efficacy in planning EOL decisions. Instruments that provide structured approaches to guide these challenging EOL conversations are needed. The Patient Preferences About Serious Illness Instrument (PASI) is a resource to normalize the conversation for practitioners and should be used in conjunction with existing advanced care planning directives such as Physician Orders for Life-Sustaining Treatments and The Five Wishes. This article introduces a new model of meaningful conversation in serious illness and provides information about how the PASI can be used to support the challenging conversations that are important for patients facing serious illness. Case examples are presented to illustrate the value of the PASI in eliciting preferences.