The process of sensitive and accurate detection of small quantities of disease biomarkers is critical for the clinical diagnosis of disease. In this regard, magnetic particles (MPs) have been widely used because of their unique magnetic properties allowing for efficient target capture, enrichment and convenient separation. These properties, coupled with great signal amplification, have enabled MP-based biosensors to achieve ultrasensitivities. Over the past few years, several ultrasensitive MP-based biosensors suitable for early clinical diagnostics have been reported. This article highlights some of the most recent developments, with a focus on MP-based ultrasensitive assays that use an antibody or aptamer as the target-binding agent, and that utilize efficient signal amplification/readout strategies.