A medical device insertion system (200, 300, 400, 2400, 2500, 2700, 3700) comprising: a sheath (242, 342, 442, 2512, 2708, 3708) defining a distal surface for placement on a skin surface of the subject, the sheath having a first at least one retention feature; a handle (302, 402, 2502, 2702, 3702) movable relative to the sheath between a proximal position and a distal position that is closer to the skin surface, the first at least one retention feature being in contact with the handle; a device support movable between a proximal position and a distal position that is closer to the skin surface, and adapted to support a medical device comprising an analyte sensor; a sharp support movable between a proximal position and a distal position that is closer to the skin surface and adapted to support a sharp (224, 324, 424, 2404, 2550); and a spring (246, 346, 446, 2406, 2544, 3746) that is expandable from a compressed state for moving the sharp support proximally towards the proximal position when the sharp support reaches the distal position; wherein the handle is adapted to urge the device support and the sharp support, and the spring while in the compressed state, from the proximal position to the distal position to insert the sharp under the skin surface, wherein advancing the handle from the proximal position to the distal position comprises applying a minimum force to overcome the first at least one retention feature in contact with the handle to allow distal movement of the handle relative to the sheath; wherein the device support includes a second at least one retention feature adapted to operatively engage the sharp support; and wherein the minimum force applied to the handle moves the sheath into the handle and moves the medical device from the proximal position to the distal position and inserts the sharp under the skin surface. a sheath (242, 342, 442, 2512, 2708, 3708) defining a distal surface for placement on a skin surface of the subject, the sheath having a first at least one retention feature; a handle (302, 402, 2502, 2702, 3702) movable relative to the sheath between a proximal position and a distal position that is closer to the skin surface, the first at least one retention feature being in contact with the handle; a device support movable between a proximal position and a distal position that is closer to the skin surface, and adapted to support a medical device comprising an analyte sensor; a sharp support movable between a proximal position and a distal position that is closer to the skin surface and adapted to support a sharp (224, 324, 424, 2404, 2550); and a spring (246, 346, 446, 2406, 2544, 3746) that is expandable from a compressed state for moving the sharp support proximally towards the proximal position when the sharp support reaches the distal position; wherein the handle is adapted to urge the device support and the sharp support, and the spring while in the compressed state, from the proximal position to the distal position to insert the sharp under the skin surface, wherein advancing the handle from the proximal position to the distal position comprises applying a minimum force to overcome the first at least one retention feature in contact with the handle to allow distal movement of the handle relative to the sheath; wherein the device support includes a second at least one retention feature adapted to operatively engage the sharp support; and wherein the minimum force applied to the handle moves the sheath into the handle and moves the medical device from the proximal position to the distal position and inserts the sharp under the skin surface.