Sometimes resetting the NIC can bring it back again:
# ifconfig em3 down; ifconfig em3 up
Faulty cable
Traffic shaping (ALTQ or Limiters) dropping the packet
Virtual NIC being throttled by the hypervisor or host, such as an AWS instance using more throughput than an instance size can support
In this case, change the throttling in the host (not guest) or upgrade to a larger instance/higher tier on a hosted platform such as AWS.
Virtual NIC being disconnected/disabled in certain hypervisors
An otherwise overloaded NIC exhausting its send/recv buffers
Other various switches/buffer/connectivity issues
Trying to bounce the NIC with ifconfig is the easiest thing to try first. After that, save/apply the interface settings on each interface (or at least WANs and the LAN in question). Check/(re)set the default route if it has been lost. Reset States. Replacing the cable may also help. Removing traffic shaping if it is enabled is also a good test.
Otherwise, investigate the traffic on the NIC and look for other buffer-related causes.