Isaac Guerendo

With Jordan Mason traded and Christian McCaffrey looking healthy heading into the season, Guerendo enters 2025 as one of the top handcuff running backs in fantasy football, provided he can hold off fifth-round rookie Jordan James for the RB2 job in San Francisco. Guerendo showed plenty of juice when given the opportunity last year, turning in 75, 102, 99, and 128 total yards in the four games where he played at least 50% of the snaps. He also ripped off 99 yards on just 10 carries in a limited role (26% of snaps) against Seattle in Week 6. He was also efficient as a receiver, posting 1.42 yards per route run—good for the 81st percentile among running backs—which bodes well for his three-down potential if pressed into service. McCaffrey has missed 20 games over the last three seasons, so the path to touches is clearer than it might seem on paper. Pending the camp battle with James, Guerendo is an elite handcuff and a perfect Zero RB target with league-winning upside if McCaffrey were to miss time.