An important measure for increasing oil and gas recovery is infill drilling. For mature fields, drilling and completion of new wells can be challenging due to a limited (or non-existent) operational window. The operational window is defined by an upper and a lower bound. The lower bound is usually based either on the pore pressure or the borehole stability limit, whichever is higher. The upper bound is an estimate of the maximum hydraulic pressure the wellbore wall can be exposed to without experiencing fluid loss (called Fracture Gradient, FG). Losses can occur in all types of reservoirs, but depleted reservoirs are more prone to losses because of reduced pore pressure and the decreasing in-situ stress. With reducing stress, the fracture propagation pressure decreases, and it becomes easier to open and drive a hydraulic fracture. A mitigating factor is to reduce mud weight, but this is not always possible in cases of differential depletion where there can be a complex distribution of pore pressure and fracturing pressure along the well. In many such cases, a FG much larger than the fracture propagation pressures in the low-pressure zones is required so that a mud weight can be selected that will balance the high-pressure zones. Such strategies then rely on the extra "strength" provided by the wellbore and specialized particles. Lost-circulation issues lead to non-productive rig time and direct costs associated with lost volumes of mud. If not managed correctly, they may also lead to loss of well/technical sidetrack and, in the worst case, serious well control incidents. Understanding the mechanisms in play is crucial for curing losses, since lost circulation materials used to treat losses caused by induced fractures are not necessarily effective against losses in naturally fractured rocks because of differences in fracture aperture and connectivity. Numerical modelling and analysis of lost-circulation mechanisms are presented in this article. Losses at so-called weak points are addressed and analysis of field data is discussed. Different potential influences on the FG are considered. Effects of varying rock properties and reservoir depletion, and different borehole geometries are modelled and discussed. Shale/sand interfaces are modelled as potential weak-zones and the resulting shear stresses across such interfaces are analyzed during drill-out. We find that such interfaces can be potential weak-zones and that boreholes with non-circular shape are more likely to experience tensile fracturing and mud losses. This highlights the challenges when estimating FG for heavily depleted reservoirs and it confirms the understanding that poor drilling practice which can create weak-points can directly reduce the FG (in addition to unfavorable ECD conditions in well).