PySerial, check if Serial is Connected
You might be able to tell whether the device is physically plugged in by checking the status of one of the RS232 control lines - CTS, DSR, RI, or CD (all of which are exposed as properties in PySerial).  Not all USB-serial adapters support any of these.
If the only connection to the device is the TX/RX lines, your choices are extremely limited:

Send a command to the device and see if it responds.  Hopefully its protocol includes a do-nothing command for this purpose.
If the device sends data periodically without needing an explicit command, save a timestamp whenever data is received, and return False if it's been significantly longer than the period since the last reception.
So I am working on a project that has a Raspberry Pi connected to a Serial Device via a USB to Serial Connector.  I am trying to use PySerial to track the data being sent over the connected Serial device, however there is a problem.
Currently, I have my project set up so that every 5 seconds it calls a custom port.open() method I have created, which returns True if the port is actually open.  This is so that I don't have to have the Serial Device plugged in when I initially go to start the program.
However I'd also like to set it up so that the program can also detect when my serial device is disconnected, and then reconnected.  But I am not sure how to accomplish this.
If I attempt to use the PySerial method isOpen() to check if the device is there, I am always having it return true as long as the USB to Serial connector is plugged in, even if I have no Serial device hooked up to the connector itself.